Tapentadol hydrochloride is the hydrochloride of tapentadol, and a novel central analgesic with dual mechanism of action developed by Johnson & Johnson Inc. in USA. It is used as medicine in the form of single isomer of (1R,2R), molecular formula: C14H24ClNO, chemical name: (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride. The structural formula is as follows:

Tapentadol belongs to the 1-phenyl-3-(dimethylamine) propane compound which has various pharmacological activities, and can be used for relieving pain (EP963475), also for treating psychosis (DE102007012165), depression (DE10233048), urinary incontinence (WO2002043715), etc.
Tapentadol hydrochloride was on the market under the approval of U.S. Food and Drug Administration on Nov. 21, 2008, and the clinic showed that it has good analgesic effect. Tapentadol hydrochloride is not only a μ opiate receptor agonist, but a norepinephrine reuptake inhibitor (Tzschentke T M, et al., J. Pharm. Exper. Therap., 2007, 323, 265), with the analgesic effect on various animal subjects suffering from acute, inflammatory and chronic neuropathic pains. Its effect is between morphine and tramadol, and the satisfied plasma drug concentration can be reached by intravenous injection or oral administration. It has good tolerance, and is difficult to produce analgesic tolerance and physical dependence compared with morphine. The side effect (especially the gastrointestinal side effect) is further improved compared with the strong opioids of the equivalent analgesic dosage, so the prospect in the treatment of acute and chronic moderate to severe pains is better and better.
The chemical structures of tapentadol and analogues thereof have been disclosed in EP-A-0,693,475 where the prepared precursor of tapentadol, (2R,3R)-3-(3-methoxy-phenyl)-N,N,2-trimethylamylamine, is obtained by continuously converting (2R,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl-3-pentanol into the relevant halide by thionyl chloride, removing the tertiary hydroxyl on (2R,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl-3-pentanol, and removing chlorine by zinc borohydride, zinc cyanoborohydride and/or tin cyanoborohydride. The defect of this process is that the halide is obtained by the excessive strong chloridizing agent, thionyl chloride. And, from the point of view of fire and health, it is too hazardous by using the hydriding reagent, such as zinc borohydride, zinc cyanoborohydride and tin cyanoborohydride, in the industrial scale.
Tapentadol is obtained by converting (2S,3S)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl-3-pentanol into the mixture of (2R,3R) and (2R,3S)-3-(3-methoxy-phenyl)-N,N,2-trimethylpentylamine by the prepared precursors in WO-2004/108658 and WO-2005/00078. The two replacement methods are characterized in that the obtained 3-(3-methoxy-phenyl)-N,N,2-trimethylpentylamine is the mixture of (2R,3R) and (2R,3S) stereoisomers and must be separated to obtain the required (2R,3R) stereoisomer.
Based on EP-A-0,693,475, the improvement has been made in CN200780028472.6 where (2R,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl-3-pentanol is subject to hydrogenolysis by a palladium catalyst. This reaction is carried out under the condition of high temperature catalysis, so the reaction condition is very rigour and the requirement on reaction equipment is higher, resulting in inconvenience for the actual production.